Gündüz Serhat, Savić Tanja, Toljić Đorđe, Angelovski Goran
MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics.
MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics;
J Vis Exp. 2016 Dec 4(118):54776. doi: 10.3791/54776.
Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance imaging (MRI). Their purpose is to enhance the relaxation rate of water protons in tissue, thus increasing the MR image contrast and the specificity of the MRI measurements. Current clinically approved contrast agents are low molecular weight molecules that are rapidly cleared from the body. The use of dendrimers as carriers of paramagnetic chelators can play an important role in the future development of more efficient MRI contrast agents. Specifically, the increase in local concentration of the paramagnetic species results in a higher signal contrast. Furthermore, this CA provides a longer tissue retention time due to its high molecular weight and size. Here, we demonstrate a convenient procedure for the preparation of macromolecular MRI contrast agents based on poly(amidoamine) (PAMAM) dendrimers with monomacrocyclic DOTA-type chelators (DOTA - 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate). The chelating unit was appended by exploiting the reactivity of the isothiocyanate (NCS) group towards the amine surface groups of the PAMAM dendrimer to form thiourea bridges. Dendrimeric products were purified and analyzed by means of nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. Finally, high resolution MR images were recorded and the signal contrasts obtained from the prepared dendrimeric and the commercially available monomeric agents were compared.
钆（III）与无环或大环螯合物形成的顺磁性配合物是磁共振成像（MRI）中最常用的造影剂（CAs）。其目的是提高组织中水质子的弛豫率，从而增加MR图像对比度和MRI测量的特异性。目前临床批准的造影剂是低分子量分子，可迅速从体内清除。使用树枝状大分子作为顺磁性螯合剂的载体在更高效的MRI造影剂的未来发展中可发挥重要作用。具体而言，顺磁性物质局部浓度的增加会导致更高的信号对比度。此外，由于其高分子量和尺寸，这种造影剂具有更长的组织保留时间。在此，我们展示了一种基于带有单大环DOTA型螯合剂（DOTA - 1,4,7,10 - 四氮杂环十二烷 - 1,4,7,10 - 四乙酸）的聚（酰胺胺）（PAMAM）树枝状大分子制备大分子MRI造影剂的简便方法。通过利用异硫氰酸酯（NCS）基团与PAMAM树枝状大分子的胺表面基团的反应性来连接螯合单元，以形成硫脲桥。通过核磁共振光谱、质谱和元素分析对树枝状大分子产物进行纯化和分析。最后，记录高分辨率MR图像，并比较从制备的树枝状大分子造影剂和市售单体造影剂获得的信号对比度。
